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Igf2-derived intronic miR-483 promotes mouse hepatocellular carcinoma cell proliferation

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Abstract

Most intronic micro-RNAs are coexpressed with their host genes, suggesting that they may play similar roles. The function of miR-483 remains unknown, although it is embedded in an intron of Igf2 gene, which is an activator of hepatocellular carcinoma proliferation. In the present study, we provide evidence that Igf2-derived miR-483 can induce proliferation in hepatocellular carcinoma cells. The miR-483 promotion of proliferation was analysed by soft agar colony formation assay and proliferation curve assay. The effect of miR-483 on Socs3 expression was examined by Western blot and a reporter assay. Our results revealed that Igf2-derived intronic miR-483 was identified by the application of 94G6, an inhibitor of Igf2 at the transcriptional level. All results from the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT assay, the proliferation curve assay and the soft agar colony formation assay showed that miR-483 promoted the proliferation of hepatocellular carcinoma cells. Finally, Socs3, a putative target predicted by bioinformatics, was regulated by miR-483 at mRNA and protein levels. Direct binding with the 3′ UTR was identified by a luciferase activity assay. Our findings demonstrate that Igf2-derived intronic miR-483, through downregulation of its target Socs3, regulates hepatoma cell proliferation and thus may serve as a potential target for hepatocellular carcinoma therapy.

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Acknowledgments

This work was supported by the Young Natural Science Foundation of Heilongjiang Province (QC2010002), the Natural Science Foundation For Youth of China (Project No. 81101373) and the Postgraduate Foundation of Heilongjiang Province (YJSCX2011-320HLJ).

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All authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, 150086, China

    Ning Ma, Fuyuan Li, Dan Li, Yang Hui, Xidi Wang, Yu Qiao, Ying Xiang, Jianying Zhou, Lingyun Zhou & Xu Gao

  2. The First Clinical Medical College, Harbin Medical University, Harbin, 150086, China

    Yanfen Zhang

  3. Beijing Institute of Radiation Medicine, Beijing, 100850, China

    Xiaofei Zheng

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  1. Ning Ma
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  2. Fuyuan Li
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  3. Dan Li
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  4. Yang Hui
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  11. Xiaofei Zheng
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Corresponding author

Correspondence to Xu Gao.

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Ning Ma and Fuyuan Li contributed equally to this work.

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Ma, N., Li, F., Li, D. et al. Igf2-derived intronic miR-483 promotes mouse hepatocellular carcinoma cell proliferation. Mol Cell Biochem 361, 337–343 (2012). https://doi.org/10.1007/s11010-011-1121-x

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  • DOI: https://doi.org/10.1007/s11010-011-1121-x

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